Feasibility study of Internet video-based speech-language activity for outpatients with primary progressive aphasia

Background Primary progressive aphasia is a clinical dementia syndrome secondary to neurodegenerative disease characterized by language-related difficulties. Currently, there is no effective treatment for language impairment in primary progressive aphasia. In the present study, we investigated the feasibility of Internet video-based speech-language activities for this condition. Methods Twenty-three people with primary progressive aphasia (pwPPA) participated in the study and were provided with twelve speech-language activity videos on a dedicated website, with three sessions per week. The group that chose to continue with participation after three months of intervention received Internet activities for one year. Cognitive domains associated with persistence, treatment motivation, and video difficulty settings were statistically analyzed. Results After three months, 17 out of 23 participants opted to continue with the activities. The ability to follow oral commands which was measured pre intervention was higher in the group that continued compared with those participants who discontinued activity. The scores of two Standard Language Test of Aphasia subtests, sentence repetition and narrative writing–associated with the ability to comprehend and produce sentence structure–were highly correlated with motivation, interest and concentration in activity. Participants with different levels of primary progressive aphasia progression could participate in the same video-based activities when high-frequency words were used in the video. Conclusions Internet video-based speech-language activity at home has potential as a useful tool for future primary progressive aphasia treatment because it provides a cost-effective approach to intensive intervention and overcomes barriers associated with traditional therapy approaches.

to-face treatment and demonstrated technology's critical role in ensuring speech-language therapy that can be implemented under these circumstances.
Therefore, this study investigated the feasibility of home-based speech-language activities for people with PPA (pwPPA) using online videos. There were concerns about the pwPPA maintaining motivation in activities conducted alone at home, and that online videos uploaded from the Internet could not be customized for each individual regarding difficulty level and video speed. Thus, we conducted an autonomous speech-language activity at home using online internet videos with the same content and speed for PPA with varying severities and symptoms, as well as the cognitive domains that influence the realization and discussed whether the content, speed, or difficulty of the video needs to be adjusted for each person. The goal of this study was not to investigate the effectiveness or efficacy of the intervention, but examine the specific uncertainties associated with conducting a larger study, such as the user acceptability or adherence to the intervention.

Participants
Twenty-three right-handed pwPPA, including 14 people with lvPPA, 6 with non-fluent and/or agrammatic variant PPA, and 3 with svPPA, were recruited from the Departments of Psychiatry at the Tokyo Medical University Ibaraki Medical Center, the University of Tsukuba Hospital and the Memory Clinic Ochanomizu between November 2020 and March 2021. The participants took part in a prospective study of speech activities at home using online videos. Clinical diagnosis of PPA was made by one of three medical doctors (SH, TA or TA) based on clinical symptoms, neurological findings, and neuroimaging examinations after the following neuropsychological examinations by the same speech-language pathologists (YK), following the PPA criteria from Gorno-Tempini et al. [2]. The group contained 15 male participants and 8 female participants. Mean (±SD) age at the time of participation was 67.7 (±10.7) years with a range of 51-87 years. Symptom duration (±SD) had a mean of 4.4±2.0 years. Mean (±SD) score for the Mini-Mental State Examination (MMSE) was 18.8±6.2, and Frontal Assessment Battery (FAB) mean score was 11.7 (±3.4). Raven's colored progressive matrices (RCPM) and the Geriatric depression scale (GDS) had mean scores of 26.9 (±6.6) and 3.9 (±2.0), respectively.

Study design and procedure
This study was a prospective observational study conducted to assess intervention. The study was approved by the Institutional Review Board of the University of Tsukuba (Registration No.R02-182) and Tokyo Medical University (Registration No.T2020-0421). Participants were those who attended one of the three medical facilities as outpatients during the period described above, were diagnosed with PPA at their first visit, and consented to participate. During the study period, the participants continued to attend outpatient clinics once every one to two months, and if they stopped attending, study participation was stopped. This was because it was not possible to collect the answer/questionnaire booklet described below. Patients with dementia who were not diagnosed with PPA were excluded, but the results of neuropsychological examinations were not part of the inclusion criteria. Although the presence of a collaborator to support speech-language activities was not a criterion for inclusion, 18 of the 23 participants had a collaborator. They gave their informed written consent to participate. Speech-language activity took place at home using online videos of approximately 10 minutes duration. Twelve videos were created with different language content to encourage comprehension, reading aloud, dictation and/or vocalization of language components, such as nouns, verbs, sentences and numbers. These language components were changed for each video. The information was presented on the screen with letters, pictures, animations and/or auditory stimuli (Table 1 and S1 and S2 Appendices). Words with high familiarity (>5.5) were used for approximately 90% of the words in the Internet videos based on a Japanese language database [15]. A "nonverbal word" was created with reference to a Sophia analysis of language in aphasia (SALA) by converting some of the mora in a real word into other ones [16]. All online videos were uploaded through Vimeo (https://vimeo.com/jp/), and one of the 12 videos was made available to participants by embedding it on a dedicated Internet homepage. The uploaded videos were replaced with new videos three times a week and were available for viewing during that time, i.e. only one video was embedded on the homepage, which contained both explanatory and homework sections (See S1-S12 Appendices) and was set up with no speed changes. All 12 videos were provided over a 4-week period, making this into one activity course. All of the videos used in this study newly created and uploaded for each session. There was no homework in this study other than watching the videos.
Participants were given an answer/questionnaire booklet and a voice recorder and asked to record themselves during speech-language activity to provide a participation record. Participants wrote the answers in the answer/questionnaire booklet for the two dictation tasks. Questionnaires were completed at the end of each activity session at home to ascertain participants' subjective impressions of each activity. When undertaking speech-language activities alone at home, it can become increasingly difficult for pwPPA to maintain their motivation, interest, and concentration. Another concerns were that the level of difficulty and the speed of the videos could not be adapted for individuals' disease progression and that they might not be able to understand the content of the task. Therefore, a questionnaire was administered to determine whether these concerns had arisen in the session. The questionnaire included a seven-point scale with five items, including "Whether or not I would like to do it again," "Whether or not it was interesting," "Whether or not I could concentrate on the task," "Whether or not the task was difficult," and "Whether the speed of the video was fast or slow." Considering that pwPPA often have difficulty -answering questionnaires, they were asked to use the 7-point scale by simply circling the appropriate place on the line, which was visually comprehensible (S1 Fig). Activity participation was confirmed according to whether the questionnaire was complete. At the end of 12 weeks (3 courses of activity), participants were asked if they wanted to continue participating in speech-language activity. Those who wished to continue could do so for up to 48 weeks (12 courses) after giving consent again. The group that wished to continue participation after the initial 12-week period was designated the 'continued' group, and the group that stopped at that point was designated the 'discontinued' group.

Statistical analysis
Because of missing values in the questionnaire items due to non-participation, the results of the questionnaire items for the entire study period were averaged for each activity and applied to the statistics. To conduct a time-series analysis of the questionnaire scores, repeated measures analyses of variance (ANOVAs) were conducted for the average questionnaire scores for each course, followed by Bonferroni's post hoc test for multiple pairwise comparisons when statistically significant. When Mauchly's sphericity test was significant, the ANOVA results were adjusted for sphericity using Greenhouse-Geisser correction. The dimensions of the five questionnaire items were reduced to two principal components by principal component analysis. Then the correlation between the principal components and the scores of neuropsychological tests was analyzed using Pearson's correlation coefficient. The results of participants' neuropsychological tests were examined with the Shapiro-Wilk test to determine if they were derived from a normal distribution. We included neuropsychological test items that followed a normal distribution, such as MMSE, RCPM, FAB, GDS, and ten sub scores of the Standard Language Test of Aphasia (SLTA), including 'Following verbal commands,' 'Speaking object names,' 'Explaining a picture story,' 'Sentence repetition,' 'Word fluency,' 'Following written commands,' 'Writing kanji words,' 'Narrative writing,' 'Dictating kanji words' and 'Calculation.' All statistical analysis was carried out using SPSS version 28.0 (IBM Corp.: Armonk, NY). As our argument about statistical significance in this study comes from an individual null hypothesis, and not a joint null hypothesis p<0.05 was considered statistically significant [17].

Factors related to persistence with speech-language activity on the Internet
Participants were asked to confirm in writing whether they would continue their participation at the end of the 12 weeks after three courses of speech-language activity. Of the 23 participants, 17 chose to continue and 6 dropped out, giving a persistence rate of 73.9%. One participant with lvPPA declined to complete the dictation task in advance because of dysgraphia, but the others were able to work on all tasks without avoiding specific ones. We examined the factors related to the three-month persistence rate. There were no statistically significant differences between the continued and discontinued groups in the percentage of PPA subdiagnostic classifications or in the presence or absence of collaborators to support speechlanguage activity (Fisher's direct probability test, p = 0.32 and p = 0.58, respectively; S1 and S2 Tables). Neuropsychiatric tests revealed no statistically significant differences in MMSE, FAB, RCPM, and GDS scores between the groups (Mann-Whitney U test, p = 0.919, p = 0.919, p = 0.658 and p = 0.354, respectively, S2 Fig). Only one of the SLTA subtests-the 'Following verbal commands' subtest-was significantly lower in the discontinued group compared with the continued group (Mann-Whitney U test, p < 0.05. Fig 1A).

Correlation between the questionnaire content and disease progression
Four participants (of the 17 in the continued group) dropped out because of hospitalization or other reasons. Thus, 13 participants were able to continue the activity for one year. Following the study design, one video was uploaded to the website, and this was changed three times a The score of 'Following verbal commands,' one of the SLTA subtests, was significantly lower in the discontinued group compared with those continuing with the activity. The two groups were classified according to whether they wished to continue the activity at the end of 12 weeks *p < 0.05 (Mann-Whitney U test). (B) The monthly participation rate shows that participation remained relatively high throughout the study. https://doi.org/10.1371/journal.pone.0288468.g001

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week. This meant that participants might miss a video, i.e., miss out on participating in some activity sessions. However, the final analysis showed that the monthly participation rate remained relatively high throughout the study period ( Fig 1B). The average questionnaire scores for each task and course are shown in S3 or S4 Figs, respectively. Based on the results shown in S4 Fig, we analyzed whether the subjective impressions of the questionnaire differed among the 12 courses. The perceived speed of the videos differed significantly among all courses (repeated measure ANOVA, p<0.05), indicating that there was some variation in the adjustment of speed in the videos we created, but the other subjective impressions such as motivation, interest, concentration, and video difficulty did not differ significantly among the courses, indicating that these subjective impressions did not change over the time course of their activities.
To make it easier to determine the data characteristics, these subjective impressions were summarized using principal component analysis. Principal component analysis revealed that the five questionnaire items could be reduced to two dimensions: a comprehensive first main component related to motivation, interest and concentration, and a second main component regarding the video speed and difficulty. Eigenvalues exceeded 1.0 for all first principal components, and for the second principal components, except for the 'Reading aloud current topics' task. No third principal components with eigenvalues above 1.0 were found for all types of tasks ( Table 2). For each activity session, we explored cognitive domains correlated with

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changes in these principal components to determine the nature of cognitive decline associated with these concerns. The correlations between the first principal component for each task and the scores of cognitive tests and SLTA subtests are shown in Table 3. Sentence repetition and narrative writing were the SLTA subtests that correlated most with the first principal component. In particular, sentence repetition from the SLTA correlated with eight of the twelve task videos but did not correlate with the first principal component of two tasks that involved repetition tasks-repetition of words and sentences, and repetition of nonverbal words (Table 3 and  The narrative writing of SLTA was correlated with the first principal components of four tasks, were also correlated with the sentence repetition of SLTA. Of these, the first principal component of the 'dictation task' task was also correlated with three additional SLTA subtests, including 'Following verbal commands,' 'Speaking object names,' and 'Explaining a picture story,' and with the MMSE. The first principal component of the 'auditory selection of letters' task correlated with FAB scores. The RCPM, a nonverbal visuospatial cognitive test, did not correlate with the first principal component of any of the tasks, even though our activity required the visual cognition of watching a video. The first principal component of the 'dysarthria training' task-the only motor system rehabilitation activity in this study-was inversely correlated with the GDS. We also analyzed the correlation between the second main component for each task and the scores of cognitive tests and SLTA subtests (S3 Table and S5S and S5T Fig). The second principal component related to video speed and difficulty. In this study, all participants received therapies at the same difficulty level and video speed, irrespective of disease progression. Nevertheless, except for the 'Repetition of nonverbal words,' no significant correlation was found between the scores of neuropsychiatric tests and the second main component. The second main component of the 'Repetition of nonverbal words' task was inversely correlated with the MMSE and word fluency subtest of the SLTA, suggesting that participants who

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maintained scores on these tests tended to perceive the video speed and difficulty for this task more strongly.

Discussion
We studied the feasibility of online video-based speech-language activities at home for outpatients with PPA. In this study, approximately 70% of the pwPPA continued activity for three months and participated in approximately 70.4% of the three weekly sessions (Fig 1B). Even in a group of pwPPA whose MMSE had declined to an average of 18.8 points, our results showed that high participation rates could be achieved. Dementia is a disease that requires multifaceted support from medical, nursing, and social services because of the decline in activities of daily living caused by cognitive impairments. Since the COVID-19 pandemic, digital transformation has accelerated in dementia care because face-to-face support is often limited. Examples include the application of the Internet of Things (IoT) and artificial intelligence to medical and nursing care, providing remote consultation [18], monitoring [19], and support for daily living [20]. Recent studies have also explored the possibility of speech-language therapy delivered through methods other than the traditional face-to-face sessions. Speech-language therapy delivered remotely by a speech-language pathologist via an Internet videoconferencing system can effectively maintain pwPPA' language function in the short term [21][22][23]. The pre-generated Internet video-based tasks employed in this study was not tailormade for individuals. An advantage of this approach is that it provides intensive therapeutic opportunities for many pwPPA with preparation by only a small number of therapists, potentially leading to high efficacy. In contrast, a potential disadvantage was that a therapist does not provide direct support, and pwPPA may not be motivated to persist with the sessions. However, the video-based activity provided in this study demonstrated a high persistence rate, possibly achieved by combining the therapy with support during outpatient visits. The role of outpatient visits in this type of situation requires further study because a protocol in which pwPPA return a booklet, which is also a participation record, to his/her physician at each outpatient visit may have been advantageous for continued participation. 'Following verbal commands,' a subtest of the SLTA, was the only cognitive and verbal function that correlated with persistence rate, suggesting this would be a cognitive function that would be helpful in incorporating pwPPA into such an intervention.
The assessment of motivation and setting the difficulty level of the video were considered important for the Internet video-based speech-language activity. Therefore, we used a questionnaire after each task session to examine the indicators of activity adherence to identify pwPPA suited to the activity based on the correlation with impairment patterns in cognitive domains. The questionnaire content was dimensionally reduced to two principal components. The first principal component was an index of motivation, interest, and concentration. Two SLTA subtests, sentence repetition and narrative writing, correlated most with the first principal component. In particular, sentence repetition was considered an important cognitive domain because it correlated with many tasks. Repetition tests are commonly used to identify phonological ability, but grammatical competence may also be required when sentences containing many clauses are used. Studies have shown that examination of sentence repetition can provide information about sentence-level abilities, including morphosyntax, verb morphology and functional words [24,25]. Narrative writing was another sub-test with many significant correlations. It examines the ability to produce sentences and writing ability. Our results suggest that pwPPA with a marked decline in the ability to comprehend and produce sentence structure have difficulty maintaining motivation, interest, and concentration for video-based speech-language task at home, even if it is a task involving only letters or words. Unexpectedly, there was no significant correlation between the first principal components of the two repetitive tasks, the SLTA subtest and sentence repetition. It should be noted that this result may be non-specific and limited to the participants of this study.
The second principal component was an index of how participants perceived the speed and difficulty of the videos. In the current study, the video playback speed was set to be unchangeable, and it was assumed that pwPPA with more severe aphasia would face more challenges with the speed and difficulty of the videos. However, neither verbal nor nonverbal cognitive domains correlated with the second principal component for most speech therapies. This was probably because the speech rate of our videos was slow enough for many participants, and the familiarity of the words used in this study was higher than average ( [15]). Thus, our results indicate that Internet videos-if selected and created appropriately-can be used by a wide range of pwPPA. In contrast, the second principal component was inversely correlated with scores on the MMSE and word fluency task for the repetition task involving nonverbal words. This finding suggests that participants who maintained their scores on these tests tended to perceive the video speed and difficulty for the task more strongly. While nonverbal word repetition primarily involves phonological short-term memory [26], verbal word repetition activates lexical representations in long-term memory, reflecting not just phonological-but also semantic-knowledge, and therefore verbal word repetition is generally more accurate than nonverbal word repetition [27]. This property-that nonverbal word repetition does not require semantic knowledge-may be the reason for the inverse correlation observed here, and nonverbal words requires caution in the use of speech-language activities for people with early PPA.
In the present study, twelve Internet video-based speech-language activity sessions were created and shared. The current study was performed as a feasibility study because the number of participants recruited at our medical institutions was not sufficient to determine the efficacy of the intervention. Because this study used a blanket approach in which all participants participated in all types of Internet video-based activities, there was concern that some types of video tasks would decrease motivation regarding activities in individuals with certain types of aphasia. Consistent with this, our results suggest that there is some Internet video content that is not appropriate for activity motivation in some pwPPA according to impairment profile. Taylor-Rubin et al. showed that motivation was more important in sustaining lexical retrieval than caregiver availability in pwPPA [28]. Therefore, future studies will need to allow pwPPA to choose therapy content that is adapted to their needs. In addition, to observe actual participation rates, this study was conducted with participants who were not forced to watch all the videos. Therefore, there is a statistical concern regarding partial participation dropouts. An additional issue in this study is the lack of feedback from the therapist when participants made errors, failed to complete tasks, or succeeded. To resolve this, future studies would need to record results, such as the percentage of correct responses, and provide opportunities for professional feedback. The results indicate a need for an intervention study to determine the therapeutic effectiveness under conditions that will allow for a stable participation rate in the future.

Conclusions
Internet video-based speech-language activities conducted at pwPPA' homes resulted in a high persistence rate and suggests the possibility of incorporating these activities into a new therapy forPPA. The ability to follow oral commands correlated with pwPPA' willingness to persist with participation. Furthermore, scores of two SLTA subtests-sentence repetition and narrative writing, likely associated with the ability to comprehend and produce sentence structure-were highly correlated with motivation, interest and concentration in several speech-language activities. People with PPA could participate in activities based on the same video irrespective of their disease progression level because the videos were created using carefully selected highfrequency words. Cognitive training using videos at home holds potential for future dementia treatment.  Table 3 and S3 Table. (TIF) S1

S1 Appendix. Sample video that is shortened version of the 'auditory selection of letters' task.
All S1-S12 videos were conceived by SH and YK and created by SH in accordance with the objectives of the task presented in Table 1. Note that the original video used in this study was approximately 10 minutes long, and English subtitles were not present in the original video.